The proposed studies are designed to enhance the understanding of immunological factors responsible for tissue damage in SLE and related diseases. The research will focus primarily on: (1) the characterization and immunochemical properties of circulating antigens, antibodies, and immune complexes; (2) factors responsible for induction of antibodies with a propensity for immune complex formation; and (3) the mechanisms whereby antibodies and immune complexes cause tissue injury and clinical disease. These studies will employ sera and tissues of patients with SLE, of dogs with a unique syndrome similar to human SLE and of humans and experimental animals who have been treated with a group of medically important drugs (procainamide, hydralazine, and isoniazid) that induce serological changes and a clinical syndrome similar to human SLE. Circulating antigens and antibodies in SLE will assayed by standard methods, although enzyme immunoassay will be the primary technique utilized for serological studies of SLE. This should provide a sensitive and versatile method for study and characterization of antibodies and immune complexes. Correlation of serological data with tissue findings using fluorescent and immunoenzymatic methods at the light and electron microscopic level should provide insight into mechanisms of tissue injury secondary to immune complex deposition. Application of these techniques to the canine LE model should provide additional data on transport of immune complexes and pathogenetic mechanisms concerning immune complex induced tissue injury. Immunologic studies on patients and experimental animals (slow and rapid acetylator phenotype) may provide information regarding mechanisms of antibody induction and immune complex formation as a reaction to exogenous agents, some of which may be environmentally important.